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  Loss of function of KIAA2022 causes mild to severe intellectual disability with an autism spectrum disorder and impairs neurite outgrowth

Van Maldergem, L., Hou, Q., Kalscheuer, V. M., Rio, M., Doco-Fenzy, M., Medeira, A., et al. (2013). Loss of function of KIAA2022 causes mild to severe intellectual disability with an autism spectrum disorder and impairs neurite outgrowth. Human Molecular Genetics, 22(16), 3306-3314. doi:10.1093/hmg/ddt187.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0018-EA63-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0018-EA6A-A
Genre: Journal Article

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 Creators:
Van Maldergem, L., Author
Hou, Q., Author
Kalscheuer, V. M.1, Author              
Rio, M., Author
Doco-Fenzy, M., Author
Medeira, A., Author
de Brouwer, A. P., Author
Cabrol, C., Author
Haas, S. A.2, Author              
Cacciagli, P., Author
Moutton, S., Author
Landais, E., Author
Motte, J., Author
Colleaux, L., Author
Bonnet, C., Author
Villard, L., Author
Dupont, J., Author
Man, H. Y., Author
Affiliations:
1Chromosome Rearrangements and Disease (Vera Kalscheuer), Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr. 73, 14195 Berlin, Germany, ou_1479642              
2Gene Structure and Array Design (Stefan Haas), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr, 73, 14195 Berlin, Germany, ou_1479640              

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Free keywords: Adolescent Adult Animals Brain/metabolism Cells, Cultured Child Child Development Disorders, Pervasive/*genetics/*metabolism Child, Preschool Gene Knockdown Techniques *Genes, X-Linked Genetic Linkage Genetic Variation Humans Intellectual Disability/*genetics/*metabolism Male Neurites/metabolism/*physiology Rats Sequence Analysis, RNA Young Adult
 Abstract: Existence of a discrete new X-linked intellectual disability (XLID) syndrome due to KIAA2022 deficiency was questioned by disruption of KIAA2022 by an X-chromosome pericentric inversion in a XLID family we reported in 2004. Three additional families with likely pathogenic KIAA2022 mutations were discovered within the frame of systematic parallel sequencing of familial cases of XLID or in the context of routine array-CGH evaluation of sporadic intellectual deficiency (ID) cases. The c.186delC and c.3597dupA KIAA2022 truncating mutations were identified by X-chromosome exome sequencing, while array CGH discovered a 70 kb microduplication encompassing KIAA2022 exon 1 in the third family. This duplication decreased KIAA2022 mRNA level in patients' lymphocytes by 60%. Detailed clinical examination of all patients, including the two initially reported, indicated moderate-to-severe ID with autistic features, strabismus in all patients, with no specific dysmorphic features other than a round face in infancy and no structural brain abnormalities on magnetic resonance imaging (MRI). Interestingly, the patient with decreased KIAA2022 expression had only mild ID with severe language delay and repetitive behaviors falling in the range of an autism spectrum disorder (ASD). Since little is known about KIAA2022 function, we conducted morphometric studies in cultured rat hippocampal neurons. We found that siRNA-mediated KIAA2022 knockdown resulted in marked impairment in neurite outgrowth including both the dendrites and the axons, suggesting a major role for KIAA2022 in neuron development and brain function.

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Language(s): eng - English
 Dates: 2013-04-242013-08-15
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1093/hmg/ddt187
ISSN: 1460-2083 (Electronic)0964-6906 (Print)
URI: http://www.ncbi.nlm.nih.gov/pubmed/23615299
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Title: Human Molecular Genetics
Source Genre: Journal
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Publ. Info: Oxford, England : IRL Press
Pages: - Volume / Issue: 22 (16) Sequence Number: - Start / End Page: 3306 - 3314 Identifier: ISSN: 0964-6906
CoNE: https://pure.mpg.de/cone/journals/resource/954925581153